PI3K/Akt signaling regulates p27kip1 expression via Skp2 in PC3 and DU145 prostate cancer cells, but is not a major factor in p27kip1 regulation in LNCaP and PC346 cells

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Abstract
BACKGROUND We compared the involvement of PI3K/PTEN/Akt signaling in the regulation of the cell‐cycle regulator p27kip1 and investigated the mechanism of PI3K/PTEN/Akt modulation of p27kip1 in the prostate cancer cell lines LNCaP, PC346, PC3, and DU145. METHODS PI3K/PTEN/Akt signaling was manipulated by wortmannin or specific siRNA. The effects on PI3K/Akt downstream effectors and p27kip1 expression were monitored on RNA and protein levels. RESULTS PI3K/Akt inhibition in LNCaP and PC346 cells hardly affected p27kip1 expression. As shown in LNCaP cells, p27kip1 expression inversely correlated with Skp2 expression, but Skp2 was not regulated by Akt. Blocking PI3K/Akt signaling in PC3 cells resulted in decreased Skp2 protein expression and increased p27kip1. Downregulation of PTEN in DU145 cells also showed PTEN/Akt‐dependent regulation of Skp2 and p27kip1. CONCLUSIONS In PC3 and DU145 cells, Skp2 is the main determinant in the PI3K/Akt‐dependent regulation of p27kip1. In LNCaP and PC346 cells, PI3K/Akt signaling is not a major factor in p27kip1 regulation.